Abstract
In light of repeated translational failures with preclinical neuroprotection-based strategies, this preclinical study reevaluates brain swelling as an important pathological event in diabetic stroke and investigates underlying mechanism of the comorbidity-enhanced brain edema formation. Type 2 (mild), type 1 (moderate), and mixed type 1/2 (severe) diabetic mice were subjected to transient focal ischemia. Infarct volume, brain swelling, and IgG extravasation were assessed at 3 days post-stroke. Expression of vascular endothelial growth factor (VEGF)-A, endothelial-specific molecule-1 (Esm1), and the VEGF receptor 2 (VEGFR2) was determined in the ischemic brain. Additionally, SU5416, a VEGFR2 inhibitor, was treated in the type 1/2 diabetic mice, and stroke outcomes were determined. All diabetic groups displayed bigger infarct volume and brain swelling compared to nondiabetic mice, and the increased swelling was disproportionately larger relative to infarct enlargement. Diabetic conditions significantly increased VEGF-A, Esm1, and VEGFR2 expressions in the ischemic brain compared to nondiabetic mice. Notably, in diabetic mice, VEGFR2 mRNA levels were positively correlated with brain swelling, but not with infarct volume. Treatment...Continue Reading
References
Jul 1, 1977·Stroke; a Journal of Cerebral Circulation·R KatzmanA G Waltz
Apr 1, 1990·Stroke; a Journal of Cerebral Circulation·S Hatashita, J T Hoff
Dec 8, 1989·Science·D W LeungN Ferrara
Dec 8, 1989·Science·P J KeckD T Connolly
Apr 1, 1989·Stroke; a Journal of Cerebral Circulation·T Tominaga, S T Ohnishi
Jan 1, 1993·Stroke; a Journal of Cerebral Circulation·T N LinC Y Hsu
Aug 1, 1996·Neurology·S SchwabW Hacke
Sep 16, 1998·Mayo Clinic Proceedings·E F Wijdicks, M N Diringer
Dec 22, 1999·Progress in Cardiovascular Diseases·G A Rosenberg
Oct 6, 2000·The Journal of Clinical Investigation·Z G ZhangM Chopp
Oct 9, 2001·The Journal of Biological Chemistry·D BéchardP Lassalle
Jun 5, 2003·Nature Medicine·Napoleone FerraraJennifer LeCouter
Jun 19, 2003·The Journal of Clinical Investigation·Yunjuan SunDavid A Greenberg
Jan 5, 2005·Seminars in Vascular Medicine·Antonio PintoGiuseppe Licata
Feb 3, 2006·Annals of Neurology·Victoria E O'CollinsDavid W Howells
Mar 10, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Ulrich Dirnagl
Dec 5, 2006·Diabetologia·B T HawkinsR D Egleton
Jul 17, 2007·Canadian Journal of Physiology and Pharmacology·Elena B OkonCornelis van Breemen
Jul 11, 2008·Blood·Jay W ShinMichael Detmar
Jul 2, 2010·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·Ji-Ping YangXin-Feng Liu
Jun 30, 2011·The Biochemical Journal·Sina KochLena Claesson-Welsh
Aug 13, 2011·Stroke; a Journal of Cerebral Circulation·Ayman ElAliDirk M Hermann
Mar 20, 2012·Stroke; a Journal of Cerebral Circulation·Albert J YooR Gilberto González
Jun 22, 2012·Annals of Neurology·Eunhee KimSunghee Cho
Dec 18, 2012·Cancer Research·Filip RoudnickyMichael Detmar
Apr 6, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Anil ZechariahDirk Matthias Hermann
Aug 8, 2013·Stroke; a Journal of Cerebral Circulation·Roshini PrakashAdviye Ergul
Feb 6, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Adviye ErgulSusan C Fagan
Mar 5, 2014·JAMA Neurology·Ain A NeuhausAlastair M Buchan
May 29, 2014·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Eunhee KimSunghee Cho
Jun 3, 2014·Journal of Neuroinflammation·Eunhee KimSunghee Cho
Jul 25, 2014·Circulation Research·Susana F RochaRalf H Adams
Oct 23, 2014·Stroke; a Journal of Cerebral Circulation·Thomas W K BatteyW Taylor Kimberly
Apr 4, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Patrick ReesonCraig E Brown
Nov 13, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Eunhee KimSunghee Cho
Mar 17, 2017·Journal of Systems and Integrative Neuroscience·Ryan C TurnerBrandon P Lucke-Wold
Citations
Apr 26, 2019·Journal of the American Heart Association·Natsue KishidaRyosuke Takahashi
Jan 23, 2020·Journal of Clinical Laboratory Analysis·Xiaomu WuZiyang Zhu
Mar 22, 2020·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Blanca Fabiola Fajardo-FregosoMónica E Ureña-Guerrero
Apr 16, 2020·Cell Communication and Signaling : CCS·Yunxiang ZhouJianmin Zhang
Aug 11, 2020·Stroke; a Journal of Cerebral Circulation·Su Jing ChanVictor Nurcombe
Feb 6, 2019·Cell Death & Disease·Yixin ZhangJohn H Zhang
Jul 18, 2019·Frontiers in Cellular Neuroscience·Alfredo Cárdenas-RiveraLuis B Tovar-Y-Romo
Dec 15, 2018·Journal of Neuroscience Research·Robert P Ostrowski, John H Zhang
May 17, 2019·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Eunhee KimSunghee Cho
Dec 6, 2019·Stem Cells and Development·Lili XiongXiaoheng Liu
Mar 22, 2020·Translational Stroke Research·Poornima VenkatJieli Chen
May 8, 2020·Translational Stroke Research·Arjun PaudyalAurel Popa-Wagner
Mar 27, 2019·Neuromolecular Medicine·Shyanne PageAbraham Al-Ahmad
Jun 27, 2020·Translational Stroke Research·Todd C PetersonMarion S Buckwalter
Sep 6, 2020·Experimental Neurology·Poornima VenkatJieli Chen
Jul 24, 2020·Neuroscience Letters·Kevin N Sheth, W Taylor Kimberly
Feb 23, 2021·Frontiers in Aging Neuroscience·Yi YaoJianzhao Luo
Jun 26, 2021·Pharmacology & Therapeutics·Sorabh Sharma, Craig E Brown
Jul 2, 2021·Stroke; a Journal of Cerebral Circulation·Il-Doo KimSunghee Cho
Aug 20, 2021·Science Advances·Eslam M F MehinaCraig E Brown